The proposed investigations will explore the relationship between the angiotensin II (ANGII) and norepinephrine (NE) in the locus coeruleus (LC) of two hypertensive models: spontaneously hypertensive (SH) rats and their normotensive Wistar Kyoto (WKY) controls; and DOC-salt rats and their Sprague Dawley controls; as they relate to the regulation of blood pressure and the pathogensis of hypertension. computerized quantitative cytomorphometry will be carried out at the light microscopic (LM) and electron microscopic (EM) levels, and will be utilized for the quantitative evaluation of cell bodies and dendrites of LC neurons, and synapses which impinge upon them. X-ray analytical electron microscopy of chromiun-tagged NE will permit the positive identification of NE in specific ultrastructural compartment in the neuronal elements of the LC. Immunocytochemical localization of ANG II will be carried out at both the LM and EM level, and further quantitative analysis of the number and pattern of varicosities and the relationship of ANG II terminals with postsynaptic elements will be achieved with computerized cytomorphometry. The specific relationships between ANG II terminals and NE neurons in LC will be explored with combined EM immunocytochemistry for ANG II and x-ray analytical EM localization and quantitation of NE. Further, NE will be measured in LC by high performance liquid chromatography with electrochemical detection (LCEC). A possible functional link between ANG II and NE neurons will also be explored by the localization of ANG II receptors in LC. These receptors will be localized with 3H ANG II and will be quantitated by EM autoradiography. In Sprague-Dawley control and DOC-salt hypertensive rats, an initial ablation of the ventromedial hypothalamus-median eminence region will be followed after 2 weeks by the LM localization of ANG II in fiber profiles and ANG II receptors, and by LCEC measurement of NE in the locus coeruleus. Through this combination of computerized cytomorphometric, ultrastructural, immunocytochemical, and neurochemical techniques, the relationship between two systems, the ANG II and noradrenergic systems in LC, which are implicated in the control of blood pressure and the pathogensis of hypertension, can be explored in a single central site with both qualitative and quantitative methods.